Stem cells have been shown to repopulate and repair tissues, organs and/or organ systems. Of interest for regenerative medicine is the use of adult or post-natal stem cells for cell-based therapies. One particular type of post-natal stem cell is an adipose-derived stem cell which is found in the connective tissues within adipose tissue. Adipose-derived stem cells have exhibited multi-potency in vitro by being able to differentiate into cardiogenic, neurogenic, osteogenic, adipogenic and chondrogenic cell types after exposure to the appropriate differentiating environment. In vivo, adipose-derived stem cells have been demonstrated to successfully form new bone and near complete calvarial continuity around the area of skull trauma.
Adipose tissue derived from the mesenchyme contains a supportive stroma that is easily isolated. As a result, adipose tissue may represent a valuable source of stem cells. Adipose tissue derives from the mesoderm and is composed of two different cell populations, mature adipose cells and the stroma vascular fraction. This fraction contains several cell types among which are pre-adipocytes. The stroma vascular fraction cells appear to have multiple mesodermal lineage capabilities in vitro, differentiating toward osterogenic, chondrogenic, and myogenic lineages in addition to adipogenic.
An increasing number of studies have isolated stem cells from adipose tissue and have been successful in differentiating them into other cell types. Collectively, these studies provide evidence that adipose tissue contains an abundant, accessible, and replenishable source of adult stem cells that can be readily isolated.
It is estimated that eight million people per year in the United States suffer from wounds caused by mechanical trauma, vascular insufficiencies or diabetes and if these wounds are left untreated, death due to infection can occur. Occasionally these wounds never fully heal and the injury or trauma site may remain open for periods ranging from months to years. These wounds require long-term medical treatment, which in addition to the devastating health implications can become costly to the patient and/or the health care system.
An incision created by a surgeon, trauma as a result of blunt force or tissue death caused by a variety of diseases all undergo a similar process of wound healing. Wound healing occurs in three distinct phases. The inflammatory phase is characterized by inflammation at the site of the trauma. This phase is critical for healing and involves extensive cell migration. The second phase of wound healing is the proliferative phase, which is marked by epithelialization, angiogenesis, granulation tissue formation and collagen deposition. Angiogenesis, which involves new capillary formation, is used to deliver nutrients and maintain granulation. Without formation of new capillaries into the wound, required nutrients fail to reach the wound resulting in a chronically unhealed wound. The third and final stage of wound healing is the maturational phase wherein fibroblasts differentiate into collagen. The disposition of the connective tissue matrix and collagen undergoes a contraction, resulting in scar tissue. Although scar formation is critical to wound healing, excessive scar formation can have additional cosmetic and/or pathologic consequences, such as keloids and/or hypotrophic scars.
Scar formation occurs in all tissues and the adverse effects of scar formation include keloid, hypertrophic scars, burn contracture and scleroderma in skin; stricture, adhesions and chronic pancreatitis in the gastrointestinal tract; cirrhosis and biliary atresia in the liver; interstitial fibrosis and bronchopulmonary dysplasia in the lung; rheumatic disease and ventricular aneurysm in the heart; retrolental fibroplasia and diabetic retinopathy in the eye; transmission loss in nerves; ankylosis and osteoarthritis in the bones and glomerulonephritis in the kidney. The ability of a wound to heal with minimal scar formation can have a profound effect on the patient and on medical or surgical practice.
Therefore there exists a medical need for methods and compositions to promote wound healing by cellular regeneration therapy.